Review
Nuclear hormone receptor co-repressors: Structure and function

https://doi.org/10.1016/j.mce.2011.08.033Get rights and content
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Abstract

Co-repressor proteins, such as SMRT and NCoR, mediate the repressive activity of unliganded nuclear receptors and other transcription factors. They appear to act as intrinsically disordered “hub proteins” that integrate the activities of a range of transcription factors with a number of histone modifying enzymes. Although these co-repressor proteins are challenging targets for structural studies due to their largely unstructured character, a number of structures have recently been determined of co-repressor interaction regions in complex with their interacting partners. These have yielded considerable insight into the mechanism of assembly of these complexes, the structural basis for the specificity of the interactions and also open opportunities for targeting these interactions therapeutically.

Highlights

► Co-repressors SMRT/NCoR act as “hub proteins”. ► SMRT/NCoR integrate transcription factor and histone modifying enzyme signaling. ► Structures of co-repressor complexes. ► Structural studies provide mechanistic, and potentially therapeutic, insights.

Abbreviations

HDAC
histone deacetylase
HID
histone interaction domain
LBD
ligand binding domain
ID
interaction domain
RRM
RNA recognition motif

Keywords

Nuclear receptor
Co-repressor
SMRT/NCoR
TBL1
GPS2
HDAC

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